Dual glucose sensitive complex for insulin delivery. Schematic of complex formation and insulin release with dual glucose-sensitive mechanisms. Glu-insulin containing the negatively charged diol moiety and PLL-FPBA containing the positively charged PBA moiety can form a complex through electrostatic attraction and PBA-diol binding. Upon exposure of the complex to a solution containing a high level of glucose, binding of glucose to the FPBA moiety instantly reduces the positive charge density on PLL-FPBA and disrupts PBA-diol bonds, resulting in immediate release of insulin . Credit: Natural biomedical engineering (2023). DOI: 10.1038/s41551-023-01138-7
A team of chemists, polymer scientists and drug delivery specialists from Zhejiang University, in collaboration with two colleagues from the University of North Carolina at Chapel Hill, developed a type of insulin ” “intelligent” which, when tested in mouse and mini-pig models, successfully regulates blood sugar levels for up to a week after a single injection.
In their article published in the journal Natural biomedical engineeringThe group describes how they created their insulin, how it works, and how it worked when administered to diabetic mice and dwarf pigs.
Type I diabetes is a chronic disease in which the pancreas produces little or no insulin. Treatment for people with the condition includes a modified diet and regular insulin injections. Many diabetics must inject more than once a day, a regimen that is both painful and difficult: the skin at injection sites tends to harden over time, making it difficult to insert a needle .
Because of these difficulties, medical researchers have continued to search for new treatment options. In this new effort, the research team developed a type of insulin that reacts with certain agents in the body, allowing automatic control of blood glucose levels over an extended period of time.
The new smart insulin is a modified form of the type of insulin already in use: researchers added gluconic acid, which, when injected into the body, turns into a complex by binding to chemicals in the blood . Such complexes result in insulin being trapped in a natural polymer, leading to alterations in signaling. Different amounts of insulin are released depending on blood sugar levels. According to the research team, this automatically releases more insulin into the blood when it is needed (for example after a meal) and less when it is not.
The researchers tested their modified insulin on three mini-pigs and five mice, all designed to suffer from diabetes. Two of the minipigs received a high dose, while the third received a low dose.
By monitoring the test animals over the following weeks, the research team found that the low-dose miniature pig had the most stable glucose regulation compared to the other high-dose miniature pigs and also compared to to control miniature pigs receiving standard daily insulin injections.
The researchers suggest that their results are promising for a new type of treatment for patients with type I diabetes. They will continue to test their smart insulin in animals and, if all continues to go well, they will move on to human trials. ‘man.
More information:
Juan Zhang et al, 1-week normal blood glucose levels in diabetic mice and minipigs via a subcutaneous dose of a glucose-sensitive insulin complex, Natural biomedical engineering (2023). DOI: 10.1038/s41551-023-01138-7
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